APPLICANT'S ABSTRACT: The relationship between alcohol use and bone metabolism is not well defined. Alcohol abuse has been associated with suppressed bone formation, low bone density, increased falls and fractures. However, there are also data to suggest that moderate alcohol intake is associated with higher bone density. The mechanism responsible for this higher bone density is unclear, although possible mechanisms include altered levels of sex hormones or sex hormone binding proteins, decreased bone turnover, hypoparathyroidism, and increased calcitonin secretion. We propose to explore the effect of varying levels of alcohol intake on different measures of bone turnover and on bone loss in a sample of n=100 males and females over the age of 25 years old who express a range of drinking behavior, including alcohol dependence. We hypothesize that moderate alcohol intake will be associated with increased bone density in men and women who have reached peak bone mass. The increased bone density will be associated with lower bone turnover, as estimated by biochemical markers. Bone loss over 18 months, particularly at the spine, will be lower in persons with moderate alcohol intake compared to alcoholics and to non-drinkers or those with relatively lower alcohol intake. Preliminary data will be obtained to determine whether the previously reported decrease in bone turnover and bone loss in persons with moderate alcohol intake is related to altered levels of sex hormones. Severe alcoholics without liver disease but with poor nutrition will have lower bone formation and lower bone density compared to moderate drinking relatives. This may be due to the direct effect of ethanol or an indirect effect due to an increase in glucocorticoid production. As a result, the rate of bone loss is expected to be greater in chronic heavy drinkers than in persons with lower alcohol intake.